scholarly journals Saikosaponin D Inhibits the Proliferation and Promotes the Apoptosis of Rat Hepatic Stellate Cells by Inducing Autophagosome Formation

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Hong Jiang ◽  
Jia Liu ◽  
Kun Zhang ◽  
Qingxin Zeng
Keyword(s):  
Flow Cytometry ◽  
Hepatic Stellate Cells ◽  
Caspase 3 ◽  
Stellate Cell ◽  
Annexin V ◽  
Stellate Cells ◽  
Double Staining ◽  
Autophagosome Formation ◽  
Proliferation And Apoptosis ◽  
Normal Rat

Objective. This study aimed to investigate the effects of saikosaponin D (SSd) on the proliferation and apoptosis of the HSC-T6 hepatic stellate cell line and determine the key pathway that mediates SSd’s function. Methods. Cell viability was detected using the CCK-8 kit. The EdU kit and flow cytometry were used to examine cell proliferation. The Annexin V-FITC/PI double staining kit and flow cytometry were used to examine cell apoptosis. Western blot analysis was performed to analyze the expression levels of LC3, Ki67, cleaved caspase 3, Bax, and Bcl2. Autophagosome formation was detected by LC3-GFP adenovirus transfection. Results. SSd inhibits the proliferation and promotes the apoptosis of acetaldehyde-activated HSC-T6 cells. SSd treatment increased the expression of cleaved caspase 3 and Bax but reduced that of Ki67 and Bcl2. The same concentration of SSd barely influenced the growth of normal rat liver BRL-3A cells. SSd upregulated LC3-II expression and induced autophagosome formation. Autophagy agonist rapamycin had the same effect as SSd and autophagy inhibitor 3-methyladenine could neutralize the effect of SSd in acetaldehyde-activated HSC-T6 cells. Conclusions. SSd could inhibit the proliferation and promote the apoptosis of HSC-T6 cells by inducing autophagosome formation.

scholarly journals Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Renwei Huang ◽  
Qunwen Pan ◽  
Xiaotang Ma ◽  
Yan Wang ◽  
Yaolong Liang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Culture Medium ◽  
Caspase 3 ◽  
Cell Function ◽  
Stellate Cell ◽  
Annexin V ◽  
Stellate Cells ◽  
Human Hepatocytes ◽  
Injury Models

Hepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of this study was to investigate the effect of HSC-derived MVs on xenobiotic-induced liver injury. Rat and human hepatocytes, BRL-3A and HL-7702, were used to build hepatocytes injury models by n-acetyl-p-aminophenol n-(APAP) or H2O2treatment. MVs were prepared from human and rat HSCs, LX-2, and HST-T6 and, respectively, added to injured BRL-3A and HL-7702 hepatocytes. MTT assay was utilized to determine cell proliferation. Cell apoptosis was analyzed by flow cytometry and hoechst33258 staining. Western blot was used for analyzing the expression of activated caspase-3. Liver injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in culture medium were also assessed. Results showed that (1) HSC-MVs derived from LX-2 and HST-T6 were positive to CD90 and annexin V surface markers; (2) HSC-MVs dose-dependently improved the viability of hepatocytes in both injury models; (3) HSC-MVs dose-dependently inhibited the APAP/H2O2induced hepatocytes apoptosis and activated caspase-3 expression and leakage of LDH, ALT, and AST. Our results demonstrate that HSC-derived MVs protect hepatocytes from toxicant-induced injury.

Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo

1998 ◽  
Vol 275 (4) ◽  
pp. G847-G853 ◽  
Author(s):  
Jacquelyn J. Maher ◽  
John S. Lozier ◽  
Myron K. Scott
Keyword(s):  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Biologically Active ◽  
Hepatic Inflammation ◽  
Protein 4.1 ◽  
Potential Sources ◽  
Normal Rat

Hepatic stellate cells are widely recognized for their contribution to liver fibrosis. This study investigated whether these cells also promote hepatic inflammation by producing neutrophil chemoattractants. Specifically, stellate cells were examined as potential sources of cytokine-induced neutrophil chemoattractant (CINC), a rat chemokine resembling human interleukin-8. Stellate cells from normal rat liver expressed little or no CINC. In culture, CINC mRNA was induced rapidly, coinciding with the phenomenon of culture activation. CINC mRNA rose 4.6-fold within 3 days and was accompanied by secretion of immunoreactive and biologically active CINC protein (4.1 ng ⋅ μg DNA−1⋅ day−1). Studies in vivo demonstrated that CINC could be induced in stellate cells during liver injury. CINC mRNA rose significantly (4- to 6-fold) in two models of liver disease, both of which cause stellate cell activation. In summary, the data indicate that CINC is induced during stellate cell activation in culture and in vivo. They suggest that stellate cell-derived CINC can promote hepatic inflammation in vivo.

scholarly journals Schisandrin B Attenuates Hepatic Stellate Cell Activation and Promotes Apoptosis to Protect against Liver Fibrosis

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6882
Author(s):  
Zhiman Li ◽  
Lijuan Zhao ◽  
Yunshi Xia ◽  
Jianbo Chen ◽  
Mei Hua ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Schisandrin B ◽  
Proliferation And Apoptosis ◽  
Induced Apoptosis ◽  
Tgf Β1 ◽  
Different Doses

The activation of hepatic stellate cells (HSC) plays a key role in the progression of hepatic fibrosis, it is essential to remove activated HSC through apoptosis to reverse hepatic fibrosis. Schisandrin B (Sch B) is the main chemical component of schisandrin lignan, and it has been reported to have good hepatoprotective effects. However, Schisandrin B on HSC apoptosis remains unclear. In our study, we stimulated the HSC-T6 and LX-2 cell lines with TGF-β1 to induce cell activation, and the proliferation and apoptosis of the activated HSC-T6 and LX-2 cells were detected after treatment with different doses of Schisandrin B. Flow cytometry results showed that Sch B significantly reduced the activity of activated HSC-T6 and LX-2 cells and significantly induced apoptosis. In addition, the cleaved-Caspase-3 levels were increased, the Bax activity was increased, and the Bcl-2 expression was decreased in HSC-T6 and LX-2 cells treated with Sch B. Our study showed that Sch B inhibited the TGF-β1-induced activity of hepatic stellate cells by promoting apoptosis.

scholarly journals Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells.

2001 ◽  
Vol 276 (50) ◽  
pp. 47744
Author(s):  
Norifumi Kawada ◽  
Dan Bach Kristensen ◽  
Kinji Asahina ◽  
Kazuki Nakatani ◽  
Yukiko Minamiyama ◽  
...  
Keyword(s):  
Peroxidase Activity ◽  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells

scholarly journals Nuclear Cathepsin F Regulates Activation Markers in Rat Hepatic Stellate Cells

2008 ◽  
Vol 19 (10) ◽  
pp. 4238-4248 ◽  
Author(s):  
Gunter Maubach ◽  
Michelle Chin Chia Lim ◽  
Lang Zhuo
Keyword(s):  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Activation Process ◽  
Type I ◽  
Activation Markers ◽  
Nuclear Activity ◽  
Cystatin B ◽  
Cathepsin F

Activation of hepatic stellate cells during liver fibrosis is a major event facilitating an increase in extracellular matrix deposition. The up-regulation of smooth muscle α-actin and collagen type I is indicative of the activation process. The involvement of cysteine cathepsins, a class of lysosomal cysteine proteases, has not been studied in conjunction with the activation process of hepatic stellate cells. Here we report a nuclear cysteine protease activity partially attributed to cathepsin F, which co-localizes with nuclear speckles. This activity can be regulated by treatment with retinol/palmitic acid, known to reduce the hepatic stellate cell activation. The treatment for 48 h leads to a decrease in activity, which is coupled to an increase in cystatin B and C transcripts. Cystatin B knockdown experiments during the same treatment confirm the regulation of the nuclear activity by cystatin B. We demonstrate further that the inhibition of the nuclear activity by E-64d, a cysteine protease inhibitor, results in a differential regulation of smooth muscle α-actin and collagen type I transcripts. On the other hand, cathepsin F small interfering RNA transfection leads to a decrease in nuclear activity and a transcriptional down-regulation of both activation markers. These findings indicate a possible link between nuclear cathepsin F activity and the transcriptional regulation of hepatic stellate cell activation markers.

Possible Therapeutic Uses of Extracellular Vesicles for Reversion of Activated Hepatic Stellate Cells: Context and Future Perspectives

2021 ◽  
Vol 21 ◽  
Author(s):  
Fahim Rejanur Tasin ◽  
Debasish Halder ◽  
Chanchal Mandal
Keyword(s):  
Liver Fibrosis ◽  
Extracellular Vesicles ◽  
Hepatic Stellate Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Target Cells ◽  
Fibrotic Liver ◽  
Paracrine Effects ◽  
Cell Therapies

: Liver fibrosis is one of the leading causes for cirrhotic liver disease and the lack of therapies to treat fibrotic liver is a major concern. Liver fibrosis is mainly occurred by activation of hepatic stellate cells and some stem cell therapies had previously reported for treatment. However, due to some problems with cell-based treatment, a safe therapeutic agent is vehemently sought by the researchers. Extracellular vesicles are cell-derived nanoparticles that are employed in several therapeutic approaches, including fibrosis, for their ability to transfer specific molecules in the target cells. In this review the possibilities of extracellular vesicles to inactivate stellate cells are summarized and discussed. According to several studies, extracellular vesicles from different sources can either put beneficial or detrimental effects by regulating the activation of stellate cells. Therefore, targeting extracellular vesicles for maximizing or inhibiting their production is a potential approach for fibrotic liver treatment. Extracellular vesicles from different cells can also inactivate stellate cells by carrying out the paracrine effects of those cells, working as the agents. They are also implicated as smart carrier of anti-fibrotic molecules when their respective parent cells are engineered to produce specific stellate cell-regulating substances. A number of studies showed stellate cell activation can be regulated by up/downregulation of specific proteins, and extracellular vesicle-based therapies can be an effective move to exploit these mechanisms. In conclusion, EVs are advantageous nano-carriers with the potential to treat fibrotic liver by inactivating activated stellate cells by various mechanisms.

scholarly journals Palmitate and Fructose Interact to Induce Human Hepatocytes to Produce Pro-Fibrotic Transcriptional Responses in Hepatic Stellate Cells Exposed to Conditioned Media

2020 ◽  
Vol 54 (5) ◽  
pp. 1068-1082
Keyword(s):  
Differential Expression ◽  
Differentially Expressed Genes ◽  
Hepatic Stellate Cells ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Human Hepatocytes ◽  
Conditioned Media ◽  
Differentially Expressed ◽  
Transcriptional Responses ◽  
Significant Differential Expression

BACKGROUND/AIMS: Excessive consumption of dietary fat and sugar is associated with an elevated risk of nonalcoholic fatty liver disease (NAFLD). Hepatocytes exposed to saturated fat or sugar exert effects on nearby hepatic stellate cells (HSCs); however, the mechanisms by which this occurs are poorly understood. We sought to determine whether paracrine effects of hepatocytes exposed to palmitate and fructose produced profibrotic transcriptional responses in HSCs. METHODS: We performed expression profiling of mRNA and lncRNA from HSCs treated with conditioned media (CM) from human hepatocytes treated with palmitate (P), fructose (F), or both (PF). RESULTS: In HSCs exposed to CM from palmitate-treated hepatocytes, we identified 374 mRNAs and 607 lncRNAs showing significant differential expression (log2 foldchange ≥ |1|; FDR ≤0.05) compared to control cells. In HSCs exposed to CM from PF-treated hepatocytes, the number of differentially expressed genes was much higher (1198 mRNAs and 3348 lncRNAs); however, CM from fructose-treated hepatocytes elicited no significant changes in gene expression. Pathway analysis of differentially expressed genes showed enrichment for hepatic fibrosis and hepatic stellate cell activation in P- (FDR =1.30E-04) and PF-(FDR =9.24E-06)
groups. We observed 71 lncRNA/nearby mRNA pairs showing differential expression under PF conditions. There were 90 mRNAs and 264 lncRNAs strongly correlated between the PF group and differentially expressed transcripts from a comparison of activated and quiescent HSCs, suggesting that some of the transcriptomic changes occurring in response to PF overlap with HSC activation. CONCLUSION: The results reported here have implications for dietary modifications in the prevention and treatment of NAFLD.

scholarly journals Identification of GDF15 as A Pro-Fibrotic Factor in Mouse Liver Fibrosis Progression

2021 ◽  
Author(s):  
Peng Qi ◽  
Ming-Ze Ma ◽  
Jing-Hua Kuai
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Hepatic Stellate Cells ◽  
Liver Tissue ◽  
Cell Activation ◽  
Stellate Cell ◽  
Neutralizing Antibody ◽  
Stellate Cells ◽  
Fibrosis Progression

Abstract Aim:To elucidate the inhibitory role of growth differentiation factor 15 (GDF15) in liver fibrosis and its possible activation mechanism in hepatic stellate cells of mice.Methods:We generated a GDF15-neutralizing antibody that can inhibit TGF-β1-induced activation of the TGF-β/Smad2/3 pathway in LX-2 cells. All the mice in this study were induced by carbon tetrachloride and thioacetamide. In addition, primary hepatic stellate cells from mice were isolated from fresh livers using Nycodenz density gradient separation. The severity and extent of liver fibrosis in mice were evaluated by Sirius Red and Masson staining. The effect of GDF15 on the activation of the TGF-β pathway was detected using dual-luciferase reporter assays and Western blotting assays.Results:The expression of GDF15 in cirrhotic liver tissue was higher than that in normal liver tissue. Blocking GDF15 with a neutralizing antibody resulted in a delay in primary hepatic stellate cell activation and remission of liver fibrosis induced by carbon tetrachloride or thioacetamide. Meanwhile, TGF-β pathway activation was partly inhibited by a GDF15-neutralizing antibody in primary hepatic stellate cells. These results indicated that GDF15 plays an important role in regulating HSC activation and liver fibrosis progression.Conclusions:The inhibition of GDF15 attenuates chemical-inducible liver fibrosis and delays hepatic stellate cell activation, and this effect is probably mainly attributed to its regulatory role in TGF-β signalling.

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